Barker, Susan Anne; (1992) Liposomes for the delivery to the lungs. Doctoral thesis (Ph.D.), University College London.

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Abstract

This thesis consists of a study characterising preformed liposomes by the novel technique of low frequency dielectric spectroscopy, and a study investigating the gamma scintigraphy and single photon emission computed tomography (SPECT) of inhaled radiolabelled liposomes in healthy human volunteers. The low frequency dielectric spectroscopy of preformed liposomes based on L-di- palmitoylphosphatidylcholine (L-DPPC) was investigated. The dielectric response is of a modified Maxwell-Wagner type, and may be split into two regions corresponding electrically to two layers in series. Physically, these regions correspond to the lipid bilayers and the external aqueous phase of the liposomal system. This allows simultaneous monitoring of changes in both phases of a liposomal system. The effect on the dielectric response of the incorporation of cholesterol into the bilayers has been investigated. By examining the dielectric response at various temperatures of liposomes containing different amounts of cholesterol, a value for the phase transition temperature of L-DPPC liposomes was obtained, which was in agreement with published values. The effects of size, concentration and orientation of the phospholipid headgroup on the dielectric response of L-DPPC liposomes were also examined. The effects of the incorporation of a model water-soluble drug, ascorbic acid, into L-DPPC liposomes were studied. The release of entrapped ascorbic acid from L-DPPC liposomes was studied by low frequency dielectric spectroscopy. An aqueous phase radiolabel, 99mTechnetium chelated to diethylene triamine penta- acetic acid (DTPA), was used to investigate the deposition and clearance of inhaled 50:50 mole% L-DPPC:cholesterol liposomes in young healthy male volunteers. The liposomes were nebulised to the volunteers and activity monitored for 24 hours post-inhalation. Approximately 43 % of the radioactivity initially deposited remained associated with the lungs 24 hours post-inhalation, representing alveolar deposited intact vesicles. SPECT images were taken and used to assess the deposition of the liposomes in a three-dimensional fashion. The SPECT images indicated that the liposomes were distributed widely throughout the lungs.

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